Desensitization of dopamine-sensitive adenylate cyclase in striatal slices was elicited by prolonged incubation in presence of dopamine, apomorphine or SKF 38393 (all 10 MuM). Alterations in receptor properties include attenuated responsiveness of adenylate cyclase to further stimulation by dopamine receptor agonists, and by NaF or cholera toxin which act directly on the regulatory subunit of adenylate cyclase. The selective D-2 receptor agonist, LY 141865, failed to desensitize dopamine-sensitive adenylate cyclase. The desensitization of dopamine-sensitive adenylate cyclase was associated with an increased phosphorylation of specific membrane protein bands.